tbuckley/cabot-search huggingface dataset:
A pilot study of the neoadjuvant use of vemurafenib plus cobimetinib in patients with BRAF-mutant melanoma with palpable lymph node metastases: Survival results.
Authors: Teresa M. Petrella, Catalin Liviu Dragos Mihalcioiu, Carolyn Nessim, Alan Spatz, Ian Watson, Frances Catriona Wright
Journal: Journal of Clinical Oncology (2023)

9579 Background: Melanoma patients with palpable nodal metastases have a very poor prognosis with the majority recurring within the first 2-3 years post-resection with survival ranging from 20-50% at 5 years. We aimed to ascertain if patients with a BRAF V600 mutation that receive vemurafenib and cobimetinib before surgery (neoadjuvantly) have a higher probability of resectability, pathologic complete response (pCR), and a lower risk of local recurrence and a longer disease free survival (DFS), distant metastatic free survival (DMFS) and overall survival (OS). Methods: This was a single arm, prospective, multi centre phase II study in patients with histologically confirmed, BRAF V600 mutated Stage IIIB and IIIC melanoma (AJCC 7 th Edition) with palpable nodal disease. Patients received vemurafenib 960mg PO BID and cobimetinib 60mg PO OD for 4 months prior to resection followed by 8 months of adjuvant therapy post-surgery. CTscans were performed at baseline and before resection and every 6 months for the first 3 years and yearly in year 4 and 5. Biopsies for correlative studies and diagnosis were performed at baseline prior to starting therapy. The primary outcomes were the proportion of patients achieving resectability, radiologic response as per RECIST and the proportion of patients achieving a pCR. Presented here are the LRFS, DMFS, DFS and OS. Results: Twenty-four patients were enrolled and received neoadjuvant vemurafenib and cobimetinib and 21 underwent resection. Following resection and pathological evaluation 12 (57%; 95% CI 34.02-78.18)) patients achieved a pCR, 8 (38%; 95% CI 18.11-61.56) had a partial pathologic response and 1 had no pathologic response. Of the 24 patients, 2 patients (8%) developed local recurrence, 6 patients (25%) developed distant metastasis, and 8 patients (33%) had either local or distant recurrences. 7 patients (29%) died due to metastatic disease. At 60 months, LRFS was 89.5% (76.7-100%), DMFS was 75.0% (59.5-94.5%), DFS was 85.7% (72.0-100%), and OS was 63.9% (95% CI 43.5-93.8). Among total 20 evaluable patients, 17 patients had CR/PR and 3 had PD/SD as best response. There was no significant difference between patients with CR/PR or SD/PD (log-rank p-value = 0.0548) with 48 month survival of 82.4% for CR/PR population compared to 33.3% with SD or PD. Conclusions: In this small phase II study, neoadjuvant vemurafenib and cobimetinib led to a higher LRFS, DMFS, DFS and OS of all resected patients with bulky nodal disease compared to historical survival rates. Clinical trial information: NCT02036086 .
Early integration of exercise into breast cancer care: The MSK healthy living program.
Authors: Kylie Rowed, Sherry Shen, Andrea Smith, Bridget Kelly, Rocco Magnoli, Stacie Corcoran, Melissa Emerzian, Kerri Ackerman, Cynthia Cruz, Erica Salehi, Cara Anselmo, Mark E. Robson, Neil M. Iyengar
Journal: Journal of Clinical Oncology (2023)

e24047 Background: In patients diagnosed with breast cancer, quality of life (QoL) has been reported to decrease during and after treatment. Physical activity (PA) mitigates adverse effects from treatment and improves QoL, and insufficient PA is associated with cancer recurrence and mortality. However, PA interventions are not included in standard cancer care. Early intervention to increase PA levels may improve QoL during active cancer therapy. The Healthy Living Program (HLP) at Memorial Sloan Kettering Cancer Center (MSK) is a lifestyle and survivorship program that engages early-stage breast cancer patients at the time of diagnosis using lifestyle risk stratification and matched referrals. We investigated whether early exercise intervention through the MSK HLP impacts QoL within the first months after cancer diagnosis. Methods: At the time of diagnosis, patients complete a lifestyle questionnaire (LQ), which is a composite of validated instruments, including the Godin Leisure Time Exercise Questionnaire (GLTEQ). Patients not meeting PA guidelines per the GLTEQ are offered a referral to an exercise physiologist (EP). The EP creates an individualized, home-based exercise program using the FITT Principle (Frequency, Intensity, Time, and Type). Patients meet with the EP every 4 weeks for 16 weeks; if exercise recommendations continue to be unmet, the program is extended. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and 36-Item Short Form Survey Instrument (SF-36) were completed at baseline (BL) and follow-up (FU). Results: 206 patients enrolled between April 2020 – September 2022, of which 72 volunteered to complete the QoL assessments (median age 53 years [range 23-84]; 11.1% ductal carcinoma in situ, 69.4% Stage 1, 16.7% Stage 2, and 2.8% Stage 3). Among these patients, 30.6% received chemotherapy, 66.7% received radiation, 83.3% received hormone therapy, and 6% declined treatment. The mean baseline FACT scores were FACT-B: 116, FACT-G: 87, and FACT-B Trial Outcome Index (TOI): 72. At FU, scores were maintained with no significant changes (means FACT-B: 117, FACT-G: 88, and TOI: 74). Improvements were observed among the subscales of the SF-36 from BL to FU. The largest improvements were observed in physical and emotional role function scores, with 26% and 15% improvements from BL to FU, respectively. Conclusions: A clinically implemented exercise intervention embedded in standard of care prevented decreases in QoL and improved physical and emotional functioning during the initial course of adjuvant breast cancer therapy. These findings support early implementation of lifestyle modification after a breast cancer diagnosis.
Anaplastic lymphoma kinase (ALK) and ROS 1– positive advanced NSCLC: A real-world institutional experience.
Authors: Stalin Chowdary Bala, Sindhu G, Rachana Chennamaneni, Meher Lakshmi Konatam, Sadashivudu Gundeti
Journal: Journal of Clinical Oncology (2023)

e21074 Background: A novel fusion gene of EML4-ALK and ROS 1 has been identified in a subset of non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 and ROS1 fusion gene demonstrate unique clinicopathological characteristics and treatment with targeted therapy led to improved survivals. Various clinical trials had shown the efficacy of ALK inhibitors, and they had become the standard of care. The real-world data of ALK inhibitors from a developing country like India is sparse and the present study was designed to analyze the incidence and outcomes of ALK positive NSCLC. Methods: Data of advanced NSCLC patients diagnosed between 2016 and 2022 with ALK and ROS1 positivity was analyzed. Detection of ALK was done by IHC or fluorescent in situ hybridization (FISH) and ROS1 was done by FISH. Results: A total of 776 advanced NSCLC patients between 2016 and 2022 were tested for ALK of which 63(8.1%) were positive. The median age at presentation was 50 years (range, 19-80 years). Of 63 patients, 34(54%) and 29(46%) were males and females. Cough (83%) was the most common symptom at presentation followed by breathlessness (73%), anorexia (59%) weight loss (59%) and chest pain (43%). The median duration of symptoms was 3 months (range, 1-18). 44(86%) patients were never smokers and 9(14%) patients had history of smoking or tobacco usage. The most common site of metastases was opposite lung (59%) followed by bone (50%), pleural effusion (41%) and brain metastasis were seen in 13(21%) patients. Adenocarcinoma was the most common histology (95%). Detection of ALK positivity was done by IHC and FISH in 45(72%) and 18(28%) patients. Of 63 patients, 52 patients received at least 4 months of treatment and were assessed for survival. First line therapy was crizotinib, chemotherapy followed by maintenance crizotinib, ceritinib, Alectinib in 40(77%), 4(7.7%), 6(11.5%) and 2(3.8%) patients respectively. At a median follow up of 14 months, the one-year progression free and overall survival was 71% and 75% respectively. The 2 year and 3-year OS were 54% and 30% respectively. Of 322 patients tested for ROS1, 9(2.8%) were positive for ROS1 translocation and received first line therapy with crizotinib. The one-year PFS and OS of ROS 1 positive patients were 75% and 89% respectively. Conclusions: ALK and ROS1 positivity was seen in 8.1% and 2.8% of advanced NSCLC patients. Majority of patients were never smokers. Opposite lung and bone were the most common site of metastases. Approximately more than half of the patients had two-year survival rate and survivals are almost similar to clinical trials. Crizotinib is well tolerated in majority of patients.
Prevention of amivantamab infusion related reactions with extended pre-infusion day oral steroid therapy.
Authors: Daniel Boon Yeow Chan
Journal: Journal of Clinical Oncology (2023)

e21083 Background: Initial results with amivantamab (ami) in CHRYSALIS-1, and ami and lazertinib (laz) regimen in CHRYSALIS-2 showed encouraging efficacy in patients whose disease progressed after standard-of-care chemotherapy, and osimertinib (osi) and platinum-based chemotherapy respectively. Infusion related reactions however were frequent; 65% all grades in both studies and 2%/7% respectively had &gt;Grade 3 infusion related reactions. An on-going trial (NCT05663866) utilising dexamethasone (dex), montelukast and methotrexate to minimise ami infusion related reactions might be unacceptable to many patients; a simpler method would be more ideal. Ami has been available in Singapore since the third quarter of 2021. Laz is not commercially available in South Asia as at Jan 2023. Methods: A single medical oncologist in private practice in Singapore managing advanced lung cancer patients collated this cohort of 7 consecutive patients treated from August 2021 to Jan 2023 with ami. Infusion day pre-medication and infusion protocol were according to the ami product insert. All patients were EGFR mutation positive and treatment-refractory with KPS &lt;2. All who were on EGFR Tyrosine Kinase Inhibitors (TKI) concomitant with ami had tolerated these agents before and upon rechallenge of the TKI. Oral dex 8mg BD for three days (starting two days before ami) was implemented for patients 5-7 after observing patients 3-4 with &gt;Grade 3 infusion related reactions. Fisher exact test evaluated the statistical significance of the difference in the incidence rate of infusion related reactions between the patients who did and did not receive pre-infusion day steroids. Results: 0/5 and 2/2 patients with and without pre-infusion day steroids respectively had infusion related reactions (p = 0.0476). Both reactions were &gt; Grade 3. Patient 4 did not have any infusion related reactions from Doses 2 to 6 once pre-infusion day dex was given. Conclusions: Premedicating with oral dex 8mg BD for 3 days starting 2 days prior to ami was able to prevent all-grades infusion related reactions. This approach should be confirmed in a larger study given the ease of such an intervention to make ami infusion safer. [Table: see text]
MajesTEC-9: A randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.
Authors: Cyrille Touzeau, Vania TM Hungria, Divaya Bhutani, Ola Landgren, Diego Vieyra, Yue Guo, Raluca Verona, Xin Miao, Mia Qi, Latisha Watkins, Priya Shah, Katherine Chastain, Ming Qi, Hang Quach
Journal: Journal of Clinical Oncology (2023)

TPS8067 Background: Despite the advance in therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) over recent years, there remains a significant unmet medical need for new, well-tolerated therapies in earlier lines for patients who have previously received an anti-CD38 monoclonal antibody and lenalidomide. Teclistamab is the first B-cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of triple class-exposed RRMM. Teclistamab redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. MajesTEC-9 (NCT05572515) is a phase 3, randomized, open-label, multicenter study comparing teclistamab with investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with RRMM. Methods: Patients aged ≥18 years with RRMM (International Myeloma Working Group [IMWG] criteria) must have evidence of progressive disease or failure to achieve a response to last line of therapy and an Eastern Cooperative Oncology Group performance status score of 0–2. All patients must have received 1–3 prior lines of therapy, including ≥2 consecutive cycles of an anti-CD38 monoclonal antibody and ≥2 consecutive cycles of lenalidomide. Those treated with prior BCMA-directed therapy will be excluded. Approximately 590 patients will be randomized 1:1 to receive either teclistamab (28-day cycles) or PVd (21-day cycles) or Kd (28-day cycles). Stratification factors include investigator’s choice of PVd or Kd, stage of disease, number of prior lines of therapy, and anti-CD38 monoclonal antibody refractory status. Treatment will continue until disease progression, death, intolerance, withdrawal of consent, or end of study, whichever occurs first. The primary endpoint is progression-free survival (IMWG 2016 criteria); secondary endpoints include overall response rate, duration of response, and overall survival. Adverse events (AEs) will be graded by Common Terminology Criteria for AEs v5.0; cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome will be graded by American Society for Transplantation and Cellular Therapy criteria. The study opened in January 2023 and enrollment is ongoing. Clinical trial information: NCT05572515 .
Who is getting screened? Estimating uninsured and underinsured women utilizing NBCCEDP screening program in a high insurance state.
Authors: David Haynes, Maria Borrero, Dame Idossa, Lauren Roach, Mckenna Haas
Journal: Journal of Clinical Oncology (2023)

e18617 Background: The National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography and other health services for underserved women. Research has shown that this national program has improved access to mammography services. However, there is limited research describing the total number of individuals eligible to utilize these services. Howard et. al., described women eligible for NBCCEDP services at the state level. Hughes et. al. have improved upon this with the introduction of geographic small-area estimation techniques that allow us to estimate individuals below the census tract level. Our work builds upon Hughes et. al., by accounting for variations in uninsured and insurance status. Methods: We used a geospatial small area estimation technique, spatially adaptive filters, to calculate standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. The American Community Survey (2010-2014) data describing the insurance status was integrated into the spatially adaptive filters to account for the likelihood that an individual is uninsured. Results: We tested three models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for all three insurance statuses, improves our estimates by reducing estimation error by 95%. We estimate that 49,914 uninsured and underinsured women are eligible to receive services within the state of Minnesota. In addition to an improved state estimate, we also provide estimates at county level to better understand the uptake of these services. Conclusions: This analysis addresses a significant gap in the literature by including secondary datasets that allow for a more accurate prediction of both the underlying population eligible to receive services and calculation of utilization rates to address programmatic goals. Spatially adaptive filters are not restricted to a specific administrative unit and insurance status provides a better screening utilization estimate.
Advancing TNBC care in the community oncology practice: Insights from a quality improvement initiative.
Authors: Jeremy Meyer Force, Hope S. Rugo, Shelby Sullivan, Ilona Dewald, Jeffrey D. Carter, Cherilyn Heggen, Kelly E. McKinnon
Journal: Journal of Clinical Oncology (2023)

e18762 Background: New and emerging treatments for metastatic triple negative breast cancer (mTNBC) are improving outcomes for patients. However, given the fast pace of innovation, staying informed about the latest clinical trial data, guideline recommendations, and adverse event management, is challenging, particularly in community-based settings. To improve the care of mTNBC patients, we conducted a quality improvement (QI) initiative across 10 community-based oncology practices. Methods: Between 9/7/2021 and 2/11/2022, we surveyed multidisciplinary oncology team members (N = 121) at 10 community oncology clinics to assess current practices, challenges/barriers, and areas for improvement in mTNBC care. Providers then participated in audit/feedback (AF) educational sessions (N = 150) where they (a) assessed system-specific practice gaps identified via the provider surveys, (b) prioritized areas for improvement, and (c) developed action plans for addressing root causes of the identified gaps. Results: Providers reported the top challenge in caring for patients with mTNBC as sequencing treatment options across multiple lines of therapy (33%). Providers participating in the AF sessions identified impact on overall survival (55%), molecular test results (49%), and impact on patient quality of life (44%) as their primary considerations when differentiating among new and emerging targeted therapies for mTNBC. Additionally, clinicians reported having the most difficulty managing gastrointestinal distress (31%), cardiotoxicity (31%), and endocrinopathies (31%) associated with novel therapies. Providers believed improved collaboration across interprofessional teams (32%) and increased patient education for aspects of supportive care (28%) would improve care for mTNBC patients. To address the identified gaps at each location, teams developed action plans to improve coordinated mTNBC care, provide patient-centered supportive care, increase testing for targeted therapies, improve symptom and adverse event management, and create standardized order sets. Conclusions: Through this QI initiative, clinical teams identified gaps/barriers in their own practices, and developed and implemented action plans for improvement. These data and actionable insights support safe, effective, and evidence-based integration of novel therapies into mTNBC care to optimize patient outcomes. Study Sponsor Statement: The study reported in this abstract was funded by an educational grant from Gilead Sciences, Inc., who had no role in the study design, execution, analysis, or reporting.
Risk factors for in-hospital mortality in cancer patients hospitalized for COVID-19.
Authors: Ziad Abuhelwa, Ahmad Y Abuhelwa, Mohammad Safi, Caleb Spencer, Mazzin Haitham Elsamaloty, Roland T Skeel, Sadik Khuder
Journal: Journal of Clinical Oncology (2023)

e18778 Background: COVID-19 pandemic has had a devastating impact on global health, causing significant mortality and morbidity. Cancer patients are particularly vulnerable to the virus, with increased risks of adverse outcomes. In an effort to understand the factors that contribute to these outcomes, our study analyzed the predictors of mortality in cancer patients who were hospitalized for COVID-19 in the United States. Methods: In this retrospective cohort study, we used the National Inpatient Sample database 2020, the largest inpatient database in the United States, to analyze adult patients (≥18 years) who were hospitalized for COVID-19 and had a cancer diagnosis, as determined by ICD-10-CM codes. The primary outcome was in-hospital mortality. Secondary outcomes included acute respiratory failure (ARF), the need for mechanical ventilation (MV), length of stay (LOS), and total charges (TC). To identify predictors of in-hospital mortality, we performed a multivariable logistic regression analysis. A sensitivity analysis was also conducted based on the type of cancer. Results were considered statistically significant if the p-value &lt; 0.05. Statistical analysis was conducted using STATA 17.0. Results: A total of 28,300 adult patients with cancer who were hospitalized for COVID-19 were included. The mean age was 71 years, with 56.8% being male and 63.6% being White. The most prevalent comorbidities were hypertension (70.1%), hyperlipidemia (44.5%), and diabetes mellitus (34.5%). The overall in-hospital mortality rate was 17.4%. About 56.9% of the patients experienced ARF and 10.1% required MV. The mean LOS and TC were 8.1 ± 8.7 days and $82,731 ± 152,297, respectively. Multivariable logistic regression analysis revealed that predictors of in-hospital mortality were age (odds ratio [OR] 1.04, 95%CI 1.03-1.05, p-value &lt; 0.001), male gender (OR 1.18, 95%CI 1.01-1.37, p-value 0.03), congestive heart failure (OR 1.35, 95%CI 1.12-1.63, p-value &lt; 0.001), chronic kidney disease (OR 1.46, 95%CI 1.21-1.76, p-value &lt; 0.001), liver disease (OR 2.41, 95%CI 1.8-3.24, p-value &lt; 0.001), and diabetes mellitus (OR 1.22, 95%CI 1.04-1.43, p-value 0.01). No racial or socioeconomic disparities were found to be associated with in-hospital mortality. Sensitivity analysis according to cancer type showed that patients with lung cancer had the highest in-hospital mortality rate (OR 1.89, 95%CI 1.22-2.92, p-value 0.004). Conclusions: The results of our study indicate that age, male gender, and the presence of certain comorbidities such as congestive heart failure, chronic kidney disease, liver disease, and diabetes mellitus significantly impact in-hospital mortality among cancer patients hospitalized for COVID-19. Notably, lung cancer patients experienced the worst outcomes. These findings provide valuable insights for clinical decision making and future research on COVID-19 in cancer patients.